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GeneBe

4-153788505-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003013.3(SFRP2):c.331A>C(p.Ile111Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SFRP2
NM_003013.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18
Variant links:
Genes affected
SFRP2 (HGNC:10777): (secreted frizzled related protein 2) This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. Methylation of this gene is a potential marker for the presence of colorectal cancer. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP2NM_003013.3 linkuse as main transcriptc.331A>C p.Ile111Leu missense_variant 1/3 ENST00000274063.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP2ENST00000274063.5 linkuse as main transcriptc.331A>C p.Ile111Leu missense_variant 1/31 NM_003013.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
74
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2024The c.331A>C (p.I111L) alteration is located in exon 1 (coding exon 1) of the SFRP2 gene. This alteration results from a A to C substitution at nucleotide position 331, causing the isoleucine (I) at amino acid position 111 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.30
Cadd
Pathogenic
28
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.017
T
MetaRNN
Pathogenic
0.80
D
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.22
Sift
Benign
0.066
T
Sift4G
Uncertain
0.050
T
Polyphen
0.68
P
Vest4
0.67
MutPred
0.70
Gain of disorder (P = 0.1681);
MVP
0.74
MPC
1.7
ClinPred
0.95
D
GERP RS
5.0
Varity_R
0.52
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-154709657; API